2.1. Sarcoidosis
Sarcoidosis is a chronic inflammatory disorder with unknown etiology, characterized by non-caseating granulomas in affected organs, in particular, the lungs, lymph nodes, skin and eyes. The disorder is typically accompanied by nonspecific depression of cell-mediated as well as humoral immune responsiveness, and by polyclonal hypergamma-globulinemia (Siltzbach, L. E., Amer. Rev. Resp. Dis. 97:1-8 (1968); Roberts, C. R. et al., Ann. Intern. Med. 94:73 (1981)). At least 90% of the patients with this multisystem disease have pulmonary manifestations characterized by chronic inflammation, granuloma formation and some cases of pulmonary fibrosis. These processes affect the alveoli, airways and blood vessels resulting in an impairment of normal gas exchange. The inflammatory process precedes the other symptoms of sarcoidosis.
CD4.sup.+ T helper (Th) cells are believed to play a central role in the pathogenesis of sarcoidosis. Such activated cells accumulate in the alveolar space, spontaneously release IL2 and proliferate at high rates in vitro and express HLA-DR, a marker of T cell activation (Hunninghake, G. et al., N. Engl. J. Med. 305:429 (1981)). The T cells in the lung which spontaneously release IL2 are primarily of the CD4.sup.+ HLA-DR.sup.+ class (Saltini, C. et al., J. Clin. Invest. 77:1962-1970 (1986)). The release of cytokines results in modulation of granuloma formation and polyclonal activation of B cells to secrete immunoglobulin (Hunninghake et al., supra). A subset of Th cells identified by a mAb designated 5/9, which detects activated T cells, was shown to predominate in the lungs of sarcoidosis patients and was responsible for the release of lymphokines and the polyclonal B cell activation (Rossi, G. A. et al., Am. Rev. Respir. Dis. 133:1086-1090 (1986)). In sarcoidosis patients with high-intensity alveolitis, T lymphocytes from lung (but not those from peripheral blood) spontaneously release IL2 in vitro and replicate at a high rate (Pinkston, P. et al., N. Engl. J. Med. 308:793 (1983)).